Reply To: Scripts 2014

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    Energy sources used to synthesise ATP
    The energy for the synthesis of ATP comes from the breakdown of foods and phosphocreatine (PC). Phosphocreatine is also known as creatine phosphate and like existing ATP; it is stored inside muscle cells.
    Phosphocreatine (PC)
    Because it is stored in muscle cells phosphocreatine is readily available to produce ATP quickly. However it is only stored in limited quantities and therefore like our ATP stores it also runs out very quickly. -It is estimated that there is only about 100g( 3.5 oz) of ATP and about 120g( 4.2 oz) of phosphocreatine stored in the body, mostly within the muscle cells.–Together ATP and phosphocreatine are called ‘high-energy’ phosphates as large amounts of energy are released quickly during their breakdown.–Because the stores of PC run out quickly other substrates that are stored in larger quantities in the body are also used to synthesize ATP. These include the sources gained from everyday foods that provide the following macronutrients:
    1. Carbohydrates
    2. Proteins
    3. Fats
    Carbohydrates are the bodies preferred source of food energy for the synthesis of ATP, with one gram of CHO providing four calories of energy. -Once digested carbohydrates are broken down into glucose and chemical reactions involving glucose then produce ATP. Glucose is always present within the blood as it circulates and provides a readily available source of energy. Too much glucose in the blood is not healthy however as it becomes thick and sticky, making it harder to flow through small blood vessels. So to ensure the blood glucose levels are healthy excess glucose that is not needed immediately to produce energy for the body is converted into a substance called glycogen and this is stored in the muscles and liver. When needed, glycogen can then be converted back to glucose for energy.
    Fats are broken down into free fatty acids (FFA) and triglycerides which can produce ATP through chemical reactions. Fatty acids either circulate in the blood or are stored as triglycerides in adipose tissue and muscle. Fat is a very energy dense nutrient, one gram of it provides nine calories of energy. Despite the large quantity of available energy that fat has it provides this energy at a much slower rate than carbohydrate. This is because the chemical reactions required for its breakdown are much more complex and time consuming.
    Protein contains four calories per gram and again provides energy at a much slower rate than carbohydrates. -Protein only makes a small contribution to energy production. However it can become a more significant energy source under periods of prolonged starvation or in ultra endurance events where other energy sources become severely depleted. -Protein is converted into amino acids. Amino acids are normally responsible for the growth and repair of body tissue but they can also be converted into glucose or -into other substances used by the aerobic energy system to synthesise ATP. It is important to note that an excess consumption of any or all of these food sources (carbohydrates, fats or proteins) does not result in more energy being produced, rather it results in the consumed excess being converted to and stored as adipose (fat) tissue.
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    Show of the Month February 15 2014
    Lycopene from tomatoes
    Psorasis-and Healing Agents
    Alternative Options to Psoraisis
    Evening Primrose and Skin Issues
    Environmental transformations of silver nanoparticles- impact on stability and toxicity
    Lycopene from tomatoes: vesicular nanocarrier formulations for dermal delivery.
    J Agric Food Chem. 2013 Jul 31;61(30):7284-93
    Authors: Ascenso A, Pinho S, Eleutério C, Praça FG, Bentley MV, Oliveira H, Santos C, Silva O, Simões S
    This experimental work aimed to develop a simple, fast, economic, and environmentally friendly process for the extraction of lycopene from tomato and incorporate this lycopene-rich extract into ultradeformable vesicular nanocarriers suitable for topical application. Lycopene extraction was conducted without a cosolvent for 30 min. The extracts were analyzed and incorporated in transfersomes and ethosomes. These formulations were characterized, and the cellular uptake was observed by confocal microscopy. Dermal delivery of lycopene formulations was tested under in vitro and in vivo conditions. Lycopene extraction proved to be quite safe and selective. The vesicular formulation was taken up by the cells, being more concentrated around the nucleus. Epicutaneous application of lycopene formulations decreased the level of anthralin-induced ear swelling by 97 and 87%, in a manner nonstatistically different from the positive control. These results support the idea that the lycopene-rich extract may be a good alternative to the expensive commercial lycopene for incorporation into advanced topical delivery systems. –PMID: 23826819 [PubMed – indexed for MEDLINE]
    Protective effect of chlorophyllin and lycopene from water spinach extract on cytotoxicity and oxidative stress induced by heavy metals in human hepatoma cells.
    J Toxicol Environ Health A. 2013;76(23):1307-15
    Authors: Yang UJ, Park TS, Shim SM
    The purpose of this study was to examine the inhibitory effects of ethanol extract of water spinach (EEWS) containing chlorophyll and lycopene on cytotoxicity and oxidative stress in liver induced by heavy metals. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay and dichlorofluorescein (DCF) assay were conducted to measure cytotoxicity and inhibition of reactive oxygen species (ROS), respectively. Cytotoxicity was prevented at a concentration of 11.7 mg/L of EEWS. Both sodium copper chlorophyllin (SCC) and lycopene in EEWS were identified by ultraperformance liquid chromatography-photodiode array-electrospray ionization-mass spectroscopy (UPLC-PDA-ESI-MS/MSn) as major components at m/z 722.64 and 535.45, respectively. The concentrations of SCC and lycopene were 0.12 and 0.04 mg from 100 g of dried powder, respectively. Approximately 99% cytotoxicity induced by Cd was inhibited by EEWS. However, the inhibitory effect attributed to generation of ROS was similar with SCC, lycopene, and EEWS. Our results indicated that EEWS was effective in reducing cytotoxicity and oxidative stress produced by heavy metals in a HepG2 cell. Data suggest that the possible mechanism underlying the preventive action of SCC might be associated with diminished absorption of metal ions by chelating and blocking metal-mediated generation of ROS, while lycopene effects may be attributed to its high number of conjugated dienes that act as most potent singlet oxygen quenchers. —PMID: 24283422 [PubMed – indexed for MEDLINE]
    Recipe—take ethanol based alcohol( vodka-brandy-Gin—cognac-or any clear based alcohol) extract the spinach in this –through either an extraction method or through a water extraction( boiling this down ) then adding alcohol afterwards to preserve and or utilize as a carrier—use tsp increments-according to the ratios they used 3 oz ( 100grams) of dried spinach
    Psorasis-and Healing Agents
    Christoph C. Geilen and Constantin E.
    Orfanos, Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Berlin-Dahlem, Germany.
    Please address correspondence and reprint requests to: Prof.Dr.Dr. Christoph C. Geilen, Klinik und Poliklinik für Dermatologie, Universitätsklinikum Benjamin Franklin, Fabeckstrasse 60-62, 14195 Berlin-Dahlem, Germany.
    Key words: Psoriasis, psoriatic arthritis, therapy, new drugs.
    Psoriasis is one of the most common skin diseases. A variety of molecular alterations has been identified in the active, lesional epidermis and dermis of psoriasis, but the pathogenesis still remains unex p l a i n e d. Th e re fo re, a l l antipsoriatic therapeutic regimens are symptomatic. Although there is no cure for psoriasis, a variety of therapeutic modalities is available to reduce the severity and increase the life quality of the patient. In cases with mild to moderate psoriasis, topical therapy (tars, dithranol, topical corticosteroids, and vitamin D derivatives) is the most ap p ro p ri ate choice for initial tre at ment. For patients with more severe, re c a l c i t rant psori a s i s , ap p l i c ation of
    UV-radiation and systemic therap i e s ( e. g. re t i n o i d s , m e t h o t rex at e, cy cl o sporine A) are available. These modalities are more e ffe c t ive than topical therapy but they are also associated with significant cutaneous and/or systemic adverse effects and a risk-benefit ratio must be taken into account. In recent ye a rs , a va riety of new app ro a ches and substances has been d eve l o p e d. Their effi c a cy and safe t y should be proven in the future.
    Psoriasis is a common, chronic, genetically determined skin disease [F4]affecting 1-3% of European and American population. Men and women are equally affected[F5]. The mean age at onset of psoriasis skin lesions is 28 years, but initial lesions may appear in very early childhood or as late as 90 years (1,2). The initial lesion is an erythematous papule topped by a silvery scale. These p apules fo rm plaques of va ry i n g shapes and patterns. Areas of the skin most commonly affected include the elbows, knees, groin, scalp, and nails. Beside the classical plaque-type psoriasis different clinical forms have to be taken into consideration: (i) psoriasis g u t t at a, small ery t h e m at o u s , fi n e scaled papules frequently generalized S-81and developing after upper respiratory infections, e.g. viral flu or streptococcal pharyngitis, (ii) psoriasis pustulosa, which may develop in patients with or without pre – existing psoriasis. Withdrawal of systemic corticosteroids is one of the main reasons of this clinical form of psoriasis but other associations include infections and drugs (e.g. lithium, b-blockers, ACE-inhibitors), (iii) psoriatic erythroderma, a rare form of psoriasis with no typical plaque or guttate lesions resulting from a progressive worsening of psoriasis in either an acute or chronic fashion, and (iv) psoriasis arthropathica. This clinical form affects approximately 5-7% of psoriatic patients. The most common type is a monoarticular, nonsymmetrical arthritis affecting mainly joints of the hands. HLA-B27 histocompatibility antigen is s t ro n g ly associated with psori at i c arthritis, Reiter’s disease, and ankylosing spondylitis (3).A variety of cellbiological, biochemic a l , and molecularbiological alterations have been identified in the active, lesional epidermis and dermis in psoriasis, but the pathogenesis of psoriasis is still unexplained (4-6). Therapeutic regimen may clear the skin lesions but relapses occur regularly and most of the patients need once a year sufficient therapy over several weeks. Without therapy the spontaneous remission rate in psoriasis is ap p rox imately 30%, whereas, the therapeutic strategies available can induce remission in 90-100%[F6] of the patients. But in the absence of a cure we do have to keep in mind the possible side effects effects of effective drugs. Therefore, a broad therapeutic repertoire is necessary to maintain patients in remission and to reduce side effects. Before initiation of all types of treatment factors that may provoce psoriasis such as alcohol intakes, infections, drugs or local mechanical irratations have to be excluded. Furthermore, all psoriasis patients need sufficient and regular skin care with emollients and moisturizers.For patients with mild to moderate psori a s i s , topical therapies are ge n e ra l ly used. This includes tars, dithranol, topical cort i c o s t e ro i d s , and vitamin D derivatives. However, for approximately one-third of psoriasis patients these treatments are insufficient and systemic t h e rapies including photoch e m o t h e ra-py are required to be applied alone or in addition. [F7]Most types of drugs used for moderate to severe psoriasis (e.g. psoralens, retinoids, methotrexate, cyclos porine A) have varying degrees of long-term toxicities. To minimize organ damage combination and/or rotational therapy may be considered for the management of psoriasis in a series of patients (7). Topical therapy Tars Tars are mainly used in combination with UV phototherapy. In 1925 W. G o e cke rman introduced this therapy schedule consisting daily application of crude coal tar followed by UVB irradiation in patients with generalized psoriasis (8). Particularly in the USA, this treatment became a standard management procedure for psoriasis for half a century. Nowadays liquid tars are mainly used, such as liquor carbonis detergens (10-20% in petrolatum) (9).Dithranol (Anthralin, Cignolin) H y d rox ya n t h racene derivat ives have held an important place in the treatment of psoriasis since in 1877 Squire reported the beneficial effect of Goa powder, an extract of the plant Ara araroba. The active compound of this natural product is chrysarobin and its synthetic substitute dithranol (1,8-dihy-droxy-9-anthrone) was introduced into the therapy of psoriasis by Unna in Germany in 1916. Up to now the topical treatment of psoriasis by increasing concentrations of dithranol (0.05% to 2%) serves as a “golden standard” in many European studies (10, 11). The best results are seen in patients with chronic plaque-type psoriasis. In contrast, dithranol is not recommended for pustular or acute, exsudative forms of the disease. Dithranol penetrates faster and in greater amounts into lesional ascompared to non-lesional skin. Therefore, a short-contact therapy has been proposed to reduce irritancy. This form of dithranol application is recommendd part i c u l a ry for use in outpat i e n t s (12). In order to reduce side effects and to increase the efficacy many dithranol-containing combination therapies have been proposed. In our department a combination of tar plus selective UV phototherapy (310-330 nm) combined with low but increasing levels of topical dithranol in petro l atum (0.125 -0.5%) is successfully used[F8]. Recently, dithranol embedded in crystalline mooglycerides (Micanol®) has become available and its efficacy in the treatment of psoriasis has been shown. Less irritation and staining are the main advantages of this new galenic preparation (13, 14).Topical corticosteroids Topical treatment of psoriasis with corticosteroids shows fast remission of the psoriatic plaques and leads to cosmetically acceptable results for the patients. This advantage, however, does not overweight the well known disadvant ages of cort i c o s t e roids such as skin atrophy, striae, purpura, bacterial and fungal infections, steroid acne, rebound phenomena, unresponsiveness for other antipsoriatic therapies, and shortening of the remission free intervall[F9]. Also,the potential for topical fluorinated lucocorticosteroids to cause significant systemic effects has been reported (15). N eve rt h e l e s s , topical cort i c o s t e ro i d s are still useful in psoriasis in three particular indications: (i) eczematous psori a s i s , (ii) ch ronic psori atic invo l vement of the palms and soles with hyperkeratotic, plaquelike lesions and fissuring, and (iii) psoriatic involvement of the scalp.In eczematous psoriasis, topical treatment for 2-5 days with hydrocortisone 1% in cream or ointment is useful to reduce irritation, but this should be foll owed by some other conve n t i o n a l antipsoriatic regimen. The use of fluorinated corticosteroids is recommended in chronic, hyperkeratotic psoriasis palmoplantaris as a pretreatment for using P U VA photoch e m o t h e rapy. In these cases fl u o ri n ated cort i c o s t e ro i d s , e. g. b e t a m e t h a s o n , m ay be used for 3-5 days. In moderate to severe psoriasis of the scalp cort i c o s t e roids are used in combination with keratolytic ointments and tar-containing shampoos over a period of 2 – 4 weeks (16, 17). Vitamin D derivatives In 1985 patients with psoriasis we re reported to respond beneficially to oral or topical administration of 1a,25-dihy d roxyvitamin D3[F10] ( c a l c i t riol) (18). Because treatment of patients with orally administered calcitriol has a narrow safety ra n ge, topical ap p l i c at i o n has been preferred (19). It was possible to manipulate the structure of calcitriol to enhance antipsoriatic characteristics and limit calcemic side effects. Most of these alterations are done by modifying side chains of calcitriol, and together with calcitriol two analogues, calcipotriol and tacalcitol, are now marketed for treating psoriasis (20-22). In different studies it has been demonstrated that the two Vitamin D analogues were better than topical corticosteroide treatment, although more side effects were noted as compared to ointments containing corticosteroids in terms of lesional and perilesional irritations. The ap p l i c ation mode is 1-2 times daily over a period of 6 weeks. Because of
    several reports of hypercalcemia resulting from excessive use of calcipotriol o i n t m e n t , the amount of calcipotri o l ointment should be limited to a maximum of 100 g per week. However, both serum and urine calcium levels returned to normal after treatment is discontinued (23). Overall, calcitriol, calcipotriol and tacalcitol appear to be safe and effective for treating moderate plaque psoriasis by local means. Phototherapy Broad-band UVB irradiation E ru p t ive types of psoriasis re s p o n d more rapidly to broad-band UVB (290 – 320 nm) irradiation as compared to ch ronic plaque-type psoriasis. Fo r choosing the initial UVB dose the patient’s minimal erythema dose (MED) has to be determ i n e d. This dose is dependent on the skin type. MED is defined as the lowest UVB dose that causes uniform erythema with distinct borders 24 h after exposure. In most centers the phototherapy protocols start with a total body dose of 80% of MED and the dose is increased in subsequent t re atments. As a ru l e, ap p rox i m at e ly 20-35 sessions are re q u i red to cl e a r psoriasis. Combination of broad-band UVB and etretinate/acitretin (0.3 – 0.5 mg/kg daily) is useful in order to reduce the doses required for clearing, both for retinoid and UVB. After 20 to 30 irra d i at i o n s , e t re t i n at e / a c i t re t i n should be administered for additional three months in order to increase the remission-free intervall (24, 25).
    Narrow-band UVB therapy-Narrow-band (311-313 nm) UV phototherapy has been shown to be superior to conventional broad-band UVB with respect to clearing and remission times (26). Furthermore, the severity of U V-induced erythema is re d u c e d, whereas, the risk for UV-induced carcinoma is discussed controversially. Narrow-band UVB has been used successfully in several combination regimens, s u ch as with dithra n o l , vitamin D derivatives or tazarotene (27-29). Combination with systemic retinoids (etretin at e / a c i t retin) increases the effi c a cy particularly in patients with hyperkeratotic plaque-type psoriasis. The schedules used are similar to those with broad-band UVB, minimal ery t h e m a dose (MED) has to be determined and the initial dose administered is 70 – 80 % of patient’s MED.
    Selective UV phototherapy (SUP) The spectrum emitted by SUP lamps ranges from 285 to 350 nm with maxima in the UVB spectrum (310-315 nm). Selective UVA/UVB irradiation in combination with liquor carbonis detergens (10% in petrolatum) and lowdose dithranol in petrolatum is used as a standard therapeutic regimen for psoriasis in our Berlin department for more than two decades. SUP can also be combined with oral retinoids reaching the same high levels of efficacy as systemic PUVA (30).PUVA photochemotherapy PUVA is the combination of oral psoralens with subsequent irradiation with long-wave UV (UVA). In the presence of UVA psoralens crosslink the cellular D NA , and ge n e rate re a c t ive ox y ge n species inducing cell damage. Different psoralens are used: 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), and 4,5’,8-tri m e t hy l p s o ralen (TMP). The administration of psoralens can be p e r fo rmed topically (bat h – P U VA , s h ower-PUVA, c re a m – P U VA) or systemically (31-33). Topical application of TMP or 8-MOP helps to avoid gastrointestinal and ocular side effe c t s , since there is no systemic photosensitization; only 8-MOP and 5-MOP are ava i l able for oral use. If a psori at i c patient appears suitable for receiving PUVA, contraindications such as e.g. p reg n a n cy, b re a s t fe e d i n g, p h o t o s e n s i-tivity disorders, history of multiple skin cancers etc. have to be excluded and together with the MED, the patient’s minimal phototoxic dose (MPD) has to be determined. As a rule , PUVA therapy is applied in two phases: fi rs t , a clearing phase and second, the maintenance ch a ra c t e ri zed by tap e ring the UV-dose and the number of sessions given per week. In most protocols the initial UVA-dose amounts 40 % of MPD measure d. European pro t o c o l s are characterized by reduced time period re q u i red for cl e a ring and lowe r cumulative UVA dose as compared to the US protocol (34, 35). The risk of patients treated with PUVA to develop non-melanoma skin cancer has been calculated to be 12 fold for squamous cell carcinoma and 4 fold for basal cell carcinoma after more than 260 PUVA treatments (36).
    Balneophototherapy–Balneophototherapy with various quantities of diluted salts combines bath water delivery with some anti-inflammatory action or with wat e rs o l u bl e photosensitizers with subsequent UVB or UVA irradiation (see PUVA). The efficacy of salt water baths containing 15% synthetic Dead Sea salt in combination with UV phototherapy was reported in patients with various skin diseases including psoriasis and in atopic dermatitis (37), however, the value of salt water baths has been discussed controversially in psoriasis. and erythrodermic types. The mode of antipsoriatic action of retinoids [F11]is not fully understood, but it seems that etretinate/acitretin promote terminal differentiation, normalize keratinocytic proliferation and modulate leukocyte functions. The dosage required for therapy is 0.5 to 1.0 mg/kg bw/day etretinate or 0.3 -0.5 mg/kg bw/day acitretin,administered in one or two daily doses with the meals over a period of 6 to 12 weeks. Etretinate/acitretin are administered alone or in combination with other additional topical modalities (e. g t a r, d i t h ra n o l , vitamin D analog u e s ) and/or with phototherapies (UVB, SUP or PUVA). In combined schedules the dose levels may be reduced to 0.3 to 0.5 m g / k g / d ay resp. 0.2 – 0.3/kg bw/day over a period of 6 weeks in order to minimize the adverse effects. The combination of systemic oral retinoids and PUVA therapy (RePUVA) is considered as a most effective treatment modality for recalcitrant severe psoriasis and the response can be maintained by lowdose retinoid therapy. In erythrodermic psoriasis a low initial dosage should be used, increasing the dose over 3 months up to 0.5 – 0.6 mg/kg/day and then maintained for 6 months. In contrast,in pustular psoriasis a high initial dosage is necessary fo l l owed by a slow decrease up to 0.5- 0.6 mg/kg/day over a period of 3 to 6 months. Maintenance is then required for 6 to 12 months. The profile of adverse effects of systemic
    retinoids is closely associated to hypervitaminosis A (mucocutaneous symptoms, alopecia, elevation of serum lipids, hyperostosis and teratogenicity). Therefore, several contraindications for retinoid therapy should be considered and the patients should be carefully monitored. Medication of oral retinoids together with tetracyclines and high doses of acetylsalicylic acid should be avoided (40-42).
    Cyclosporine A–Cyclosporine A is a lipophilic peptide of fungal origin with profound immunosuppressive effects. It was first used in kidney, heart, and liver transplantations. Its therapeutic effect in psoriasis was shown as early as in 1979 (43). Since then nu m e rous clinical studies h ave demonstrated the effi c a cy of cy cl o s p o rine A in psoriasis. Cycl osporine A decreases interleukin-2 production of T-lymphocytes by inhibiting c a l c i n e u ri n – m e d i ated signaling pat h-ways. Beside this inhibition, cyclosporine A exerts various effects on other cells of the immune system, it disrupts the self-perpetuating process between immune cells and keratinocytes involved in psoriasis. The rapid therapeutic action and weak myelotoxicity are seen as key advantages for the use of cyclosporine A; nevertheless, nephrotoxicity and high rates of relapse after treatment cessation limit its use to patients re f ra c t o ry to other therapies. Seve ra l multicenter studies have demonstrated a dose-dependent response of psoriasis and on the basis of these findings , initial dosages of 2.5 to 5 mg/kg/day have been suggested (44).
    Fumaric acid derivatives The beneficial effect of fumaric acid derivatives in psoriasis has been first reported by the chemist Sch we cke n-diek in Germany. In a recent multicentre study an overall efficacy of 80% was shown after four months treatment with fumaric acid esters, however, adverse events (e.g. gastrointestinal complaints, flush, lymphocytopenia) were reported in 69% of the patients (45). I m mu n o h i s t o l ogical studies pointed out that systemically administered fumaric acid esters reduce infiltrating Tlymphocytes in the skin, followed by a reduction of acanthosis and parakeratosis. The recommended dosage of fumaric acid esters follows an established, i n c reasing schedule (maximum dose 1.2g per day) whereby the dose levels should be indiv i d u a l ly adjusted after clinical response. The following laboratory parameters should be monitored monthly in the first 6 months: serum c re at i n i n e, blood urea nitroge n , l ive r e n z y m e s , blood cell count incl u d i n g white cell differential count (46). Fumaric acid esters should not be combined with UV phototherapy, other immunos u p p re s s ives or potential nep h ro t ox i c d rugs. A ra n d o m i ze d, d o u bl e – bl i n d, p l a c eb o – c o n t rolled short – t e rm study also revealed the efficacy and safety of fumarates also in psoriatic arthritis (47).–unrelated chemically to cyclosporine A but also inhibits helper T-lymphocyte activation and the synthesis and secretion of cytokines. Furthermore, it has a similar toxicity profile, therefore, patients with nephrotoxicity from cyclosporine are probably not suitable candid ates for tacro l i mus because it also causes hypertension and renal insuffic i e n cy. Systemic (0.1 mg tacro l i mus per kg daily) as well as topical (0.1% tacrolimus ointment) administration of t a c ro l i mus have been rep o rted to be sufficient to improve psoriasis. However, in contrast to atopic dermatitis topical tacrolimus showed a limited efficacy in psoriasis (58, 59).
    Alefacept (B-9273)Alefacept is an LFA-3-Ig fusion protein that binds to CD 2 receptor on T-lymp h o cy t e s , inhibiting their activat i o n into CD45Ro + memory T-cells. On the background that psoriasis plaques are characterized by an infiltration of memory effector T-lymphocytes, the effect of alefacept on psoriasis was studied in a mu l t i c e n t e r, ra n d o m i ze d, p l a c eb o c o n t ro l l e d, d o u bl e – blind study. 229 Patients with chronic psoriasis received 0.025,0.075 or 0.150 mg alefacept/kg body weight or placebo intraveneously weekly over a period of 12 weeks, with follow-up for additional 12 weeks. The s t u dy revealed considerable improvement in the alefa c ept groups (38%, 5 3 % , and 53% re s p e c t ive ly ) , gre at e r than in the placebo group (21%) (60). Overall, a ‡75% PASI score reduction occurs in 25 – 30% of the treated patients, indicating that alefacept is less effective in psoriasis than methotrexate or cyclosporine.
    Infliximab-A growing body of data supports the role of the proinflammatory cytokine tumor necrosis factor (TNF) alpha in the pat h o p hy s i o l ogy of psoriasis and psoriatic arthritis since elevated TNF alpha levels are detectable in psoriatic skin lesions as well as in the joints of
    patients with psoriatic arthritis. In order to target the TNF alpha system, a chimeric monoclonal anti-TNF alpha anti-body (infliximab) has been developed. In first trials, this antibody was used in order to treat rheumatoid arthtitis and Crohn’s disease. The efficacy of infliximab in patients with psoriasis has been
    reported and a double-blind, randomised trial has been published recently. Of 33 patients enrolled, three dropped out, 9/11 (82%) patients receiving 5 mg i n fl i x i m ab/kg at weeks 0, 2 and 6 re s p o n d e d, and 10/11 (91%) pat i e n t s receiving 10 mg/kg at weeks 0, 2, and 6 responded. In both groups the median time to response was four weeks. A successful therapy of seve re re c a l c itrant psoriasis has also been reported with a combination of infliximab and methotrexate (61-63). However, severe side effects has been reported such as reactivation of tuberculosis (64, 45).
    Etanercept-An other TNF alpha neutralising agent is a TNF alpha receptor fusion protein (etanercept). The antiinflammtory action of etanercept has been first reported in rheumatoid arthritis and Crohn’s disease. In a randomised, double-blind, p l a c eb o – c o n t rolled clinical trial the efficacy and safety of etanercept in psoriasis patients was investigated. Thirty patients we re tre ated with etanercept (25 mg subcutaneously twice weekly) over a period of 12 weeks and compared with 30 placebo-treated patients. An improvement of psoriasis wa s achieved in 26/30 (87%) of etanercept-treated patients compared to 7/30 (13 %) of the controls. Further reports on a positive effect of etanercept in psoriasis and psoriatic arthritis were published re c e n t ly (66-68). Safety issues are a concern because of the ubiquitous role of TNF alpha. At the moment infections occured at the same rate and with the same frequency as in the placebo population. There should be caution in using anti-TNF agents. In general they should not be administered to patients with serious or re c u rrent infections or in pat i e n t s with untreated or latent tuberculosis.
    Leflunomide–Leflunomide is a novel immunomodu -latory compound which has been proved for the therapy of active rheumatoid arthritis in several countries. The active metabolite inhibits proliferation of activated T- and B-lymphocytes predominantly through inhibition of the de novo biosynthesis of pyrimidine nucleotides (69). Very recently, the successful treatment of a patient with severe psoriasis and psoriatic arthritis with leflunomide (10 mg daily) in combination with prednisolone (10 mg daily) and topical Vitamin D3 analogues was rep o rt e d (70).
    Pimecrolimus (SDZ ASM 981)-The ascomycin macrolactam derivative pimecrolimus is a cell-selective inhibitor of pro – i n fl a m m at o ry cy t o k i n e s and has been found to be effective in T- lymphocyte-driven skin diseases. In a first study, 15 patients were treated topically with pimecrolimus, a potent halogenated corticosteroid or vehicle . All patients treated with pimecrolimus or the corticosteroid showed a significant improvement of psoriatic lesions. This was confirmed by a further study comparing topical pimecrolimus (0.3% and 1.0%) and cl o b e t a s o l – 1 7 – p ro p i o n at e intment (0.05%) (70, 71) DAB389IL-2 (denileukin diftitox) The fusion protein DAB389IL-2 is composed by human interleukin-2 and fragments of diphtheria toxin. It bl o ck s selectively the proliferation of activated ly m p h o cytes by binding to the IL-2 receptor (CD 25). The mechanism of action is the specific toxic effect after i n t e rn a l i z ation of the re c ep t o r / f u s i o n protein complex. In a phase II multicenter trial, psoriatic patients received 5,10, or 15 µg DAB389IL-2 /kg or placebo daily intravenously for three consecutive days each week for four consecutive weeks. The degree of improvement for treated patients was significantly greater than for placebo-treated patients. However, DAB389IL-2 was not well tolerated at this dosing regimen
    Interleukin 10-The anti-infl a m m at o ry and immu n os u p p re s s ive cytokine interl e u k i n – 1 0 (IL-10) has been investi gated in patients with moderate to severe psoriasis in one pilot trial and two phase II studies and its administration was well tole rat e d. IL-10 was injected subcuta
    New developments and innovative therapies
    Tazarotene-Tazarotene belongs to the new group of receptor-selective retinoids binding to the retinoic acid receptor (RAR) family members (48, 49). A beneficial response of stationary, plaque-type psoriasis by topical tazarotene (0.05-0.1% gel) has been reported recently (50). However, topical retinoids are more potent in combination with phototherapy or with mild topical corticosteroids in order to avoid retinoid-induced irritation (51).
    Mycophenolate mofetil -Several case reports have shown that the new immunosuppressive drug mycophenolate mofetil has a good therapeutic effect in patients with psoriasis ( 5 2 ,53). Mycophenolic acid (MPA ) the active metabolite of mycophenolate mofetil, reversibly blocks the de novo biosynthesis of guanine nu cl e o t i d e s required for DNA and RNA synthesis. Therefore, all cell types that rely predominantly on this pathway, such as T-and B-lymphocytes, are most significantly affected. Mycophenolate mofetil is a morpholinoester of mycophenolic acid found to be effective in patients with severe psoriasis in the 1970s (54). Mycophenolate mofetil has better bioavailability and thus an improved therapeutic window and it has been initially applied to prevent acute rejection after renal and cardiac transplantation. Also, oral MMF (dosage: 2g daily) has been shown to be safe and effective for treating severe psoriasis (55). This new im-
    mu n o s u p p ressant may be especially useful in patients with contra i n d i c ations for other systemic antipsori at i c drugs or in patients not responding to e s t ablished antipsori atic therapy. In two recent clinical trials, the topical effect of mycophenolic acid and mycop h e n o l ate mofetil was inve s t i gat e d s h owing that my c o p h e n o l ate mofe t i l may exert an antipsoriatic effect when applied topically, whereas mycophenolic acid was not effective (56, 57).
    Tacrolimus (FK506)-Tacrolimus belongs to the group of macrolides like ascomycine and rapamycine. This immunosuppressive drug is Systemic therapy
    Methotrexate–In 1951, Guber and co-workers noted the rapid clearing of psoriasis after systemic therapy with aminopterin, but this drug was later replaced by a more stable derivative, methotrexate. Methotrexate ( 4 – a m i n o – 1 0 – m e t hy l p t e roy l g l u t a m i c a c i d, MTX) belongs to the group of antimetabolites competing with natural substances for specific enzymes usually showing greater affinity to the target. As a folic acid antago n i s t , m e t h o t rex at e inhibit DNA synthesis and to a lesser
    extent RNA synthesis. It targets, therefore, cells especially in the S-phase of the cycle. Kinetic studies in psoriasis indicated that more keratinocytes are in the S-phase than in normal skin and since this process can be reversed by methotrexate epidermal proliferation is normalized in psoriasis. Methotrexate is i n d i c ated in re c a l c i t rant disease not responsive to other regimens such as systemic adiministration of retinoids or PUVA, especially in patients with assoc i ated art h ro p at hy. Contra i n d i c at i o n s are significant abnormalities of the liver or renal function, severe anemia, leukopenia, or thrombocytopenia, female or male fertility, gastritis, active infectious diseases and ex c e s s ive alcohol consumption (38). Methotrexate can be used by oral medication (single dose 25-35 mg per week or 5-7.5 mg at 12h intervals for three doses per week) or as intramuscular injection (25-35 mg per week). In respect to the cumulative total MTX dose several studies indicated that the incidence of cirrhosis is low if the total dose of MTX does not exceed 1.5 -2.0 g. Major causes for acute methotrexate toxicity are impaired renal function and concomitant intake of tri m e t h oprim-sulfamethoxazole. A potent antidote in such cases is leucovorin calcium to be given early orally or parenterally (10 mg/m2). In treating patients with psoriasis with MTX the goal is not to achieve complete clearing, but to adequately control the disease and return to other therapeutic modalities (39), if possible to topical treatments alone.
    Etretinate/acitretin Oral retinoids are potent antipsoriatic drugs, p a rt i c u l a rly in seve re pustular neously over 3-7 weeks and a clinical efficacy was reported in the majority of patients. This possible novel therapeutic approach has to be further investigated in larger, controlled clinical trials (75). Lasers D i ffe rent ap p ro a ches of tre atment of chronic plaque-type psoriasis by lasers h ave been publ i s h e d. Wh e reas CO2 laser re s u r facing of psori atic plaques was ineffe c t ive, the 308-nm ex c i m e r laser has been shown re c e n t ly to be effective. In a pilot dose-response study i nve s t i gating 13 patients with stabl e plaque-type psoriasis cl e a ring of the lesions was rep o rt e d. Laser therapy may become an alternative for limited p s o riasis only, h oweve r, f u rther controlled trials are required (76, 77).
    In conclusion, the various regimen for psoriasis all have their relative advan-
    tages and disadvantages, whereby combinations resp. rotation of therapeutic
    means may be chosen in an attempt to i m p rove their long lasting effi c a cy,
    safety, and tolerab i l i t y. A c c o rding to the type and severity of psoriasis and
    the patient’s individual needs, therapies a re to be care f u l ly selected by the
    physician. A broad spectrum of established antipsori atic agents are now
    available and an increasing number of new drugs is being developed. Their
    clinical benefit will be determined in the near future.
    Alternative Options to Psoraisis
    Bovine Cartilage may alleviate Psoriasis (due to Glycosaminoglycans): [more info]-One human study demonstrated that of 38 patients with severe total-body Psoriasis who received subcutaneous injections of Bovine Cartilage, 50% experienced complete remission within two months with complete disappearance of lesions for an average of five months.
    Shark Cartilage may alleviate Psoriasis. references
    Bee Products
    Propolis (900 mg per day) may alleviate Psoriasis in approximately 33% of patients. references
    High consumption of (fresh) Fruit may be associated with a lowered incidence of Psoriasis. references
    Aloe vera (0.5% extract applied topically via a suitable skin-penetrating carrier vehicle such as ointment, cream or shampoo) may cure some cases of Psoriasis: references–Where Psoriasis afflicts the Scalp, topically-applied Aloe vera ointment can be used in conjunction with an Aloe vera Shampoo in order to further enhance its effectiveness.
    Barberry (ointment applied topically or capsules/extract consumed orally) may inhibit the excessive differentiation of Keratinocytes that is associated with Psoriasis (due to the Berbamine, Berberine and Oxycanthine content of Barberry). references
    Boswellia (extract) may alleviate the Inflammation associated with Psoriasis. [more info]
    Burdock (root) reputedly alleviates Psoriasis (according to folklore). [more info]
    Calendula (applied topically) may alleviate Psoriasis. [more info]
    Chamomile (ointment applied topically – especially Camocare topical ointment) may help to repair the Skin damage caused by Psoriasis (due to Chamomile’s Levomenol content). [more info]
    Coleus may alleviate Psoriasis (due to its Forskolin content increasing the body’s cAMP levels which are often depleted in Psoriasis patients). [more info]
    Comfrey (ointment applied topically) may alleviate Psoriasis (possibly due to Comfrey’s Allantoin content). references
    Goldenseal may inhibit the excessive differentiation of Keratinocytes that is associated with Psoriasis (due to the Berberine content of Goldenseal). [more info]
    Gotu Kola (cream applied topically) may accelerate the healing of Psoriasis (by enhancing the production of Cyclic AMP which facilitates Cell maturation). references
    Khella (100 mg per day orally or Khella gel applied topically) may alleviate Psoriasis. references
    Milk Thistle may alleviate Psoriasis (due to the Silymarin content of Milk Thistle). The means by which Milk Thistle may alleviate Psoriasis involves several mechanisms including: references–Improving the function of the Liver in a way that facilitates the removal of Lipopolysaccharides (endotoxins) from the body via the Liver – Lipopolysaccharides are involved in Psoriasis.
    Inhibiting the Lipoxygenase enzyme, thereby reducing the production of certain detrimental Leukotrienes that may be involved in Psoriasis.
    Lowering cyclic GMP (cGMP) and raising cyclic AMP (cAMP) (Psoriasis patients generally have a high cGMP:cAMP ratio.
    Neem (seed oil applied topically and leaf extract consumed orally) may alleviate Psoriasis. [more info]
    Olive Leaf (extract) may improve the condition of many Psoriasis patients (according to physician’s observations). [more info]
    Oregon Grape may inhibit the excessive differentiation of Keratinocytes that is associated with Psoriasis (due to the Berbamine, Berberine and Oxycanthine content of Oregon Grape). references
    Polypodium leucotomos may alleviate Psoriasis (by inhibiting the excessive activity of TH1 Helper T-Cells that occurs during Psoriasis). references
    Red Clover reputedly reduces the discomfort associated with Psoriasis (according to folklore). [more info]
    Sage (tea applied topically) may alleviate the Itching associated with Psoriasis. [more info]
    Sarsaparilla may alleviate the symptoms of Psoriasis (due to Sarsaparilla’s Sarsaponin content). references
    Yellow Dock may alleviate Psoriasis. [more info]
    Oils (dietary oils)
    Flax Seed Oil may alleviate Psoriasis (due to Flax Seed Oil’s high Alpha-Linolenic Acid (LNA) content). [more info]
    Shark Liver Oil (2,000 mg per day) may alleviate Psoriasis (due to the Alkylglycerols content of Shark Liver Oil helping to reduce the excessive proliferation of Skin Cells that occurs in Psoriasis patients and by enhancing the function of the Immune System in a way that benefits Psoriasis patients). references
    Oils (topical oils)
    Apricot Kernel Oil (applied topically) may reduce the flaking associated with Psoriasis. [more info]
    Jojoba Oil (applied topically) may alleviate the irritation associated with Psoriasis. [more info]
    Lavender (oil applied topically to affected areas or used as a shampoo on the Scalp) may alleviate the irritation associated with Psoriasis. [more info]
    Oregano Oil (applied topically) may alleviate Psoriasis. references
    Sesame Seed Oil (applied topically) may alleviate the flaking associated with Psoriasis. [more info]
    Tamanu Oil (applied topically) reputedly alleviates Psoriasis. references
    Tea Tree Oil (as an ingredient in Shampoo) may alleviate the Itching associated with Psoriasis where Psoriasis affects the Scalp. [more info]
    Wheat Germ Oil (applied topically) may alleviate Psoriasis. [more info]
    Processed Foods
    Cider Vinegar (applied topically or in a bath) has been claimed to temporarily alleviate Psoriasis. [more info]
    Bitter Melon may be beneficial for the treatment of Psoriasis (due to its ability to inhibit the activity of Guanyl Cyclase, an enzyme that is over-active in many Psoriasis patients).
    High consumption of Carrots may be associated with a lowered incidence of Psoriasis. references
    Garlic may inhibit the Lipoxygenase pathway of Arachidonic Acid metabolism which is implicated in Psoriasis. [more info]
    Onion may inhibit the Lipoxygenase pathway of Arachidonic Acid metabolism which is implicated in Psoriasis. [more info]
    Rhubarb (juice) may alleviate the Itching and Pain associated with Psoriasis (due to Rhubarb’s Anthraquinones content). [more info]
    High consumption of Tomato has been associated with a lowered incidence of Psoriasis. references
    Bathing in Sea Water may provide temporary relief of the symptoms of Psoriasis. [more info]
    Water (6 – 8 glasses daily) may improve the elimination of the toxins that are associated with Psoriasis. [more info]
    Other Therapies that may be Beneficial for Psoriasis
    Electromagnetic Radiation
    The Ultra-Violet Radiation in Sunlight may temporarily alleviate the symptoms of Psoriasis: [more info]-Exposure of afflicted areas of the Skin to UV-B may temporarily alleviate Psoriasis. UV-B has been shown to inhibit the excessive proliferation of Skin Cells that occurs in Psoriasis. Its effectiveness is described as being equal to that of PUVA therapy with fewer side effects. references
    Fasting may improve the condition of Psoriasis patients (probably by decreasing levels of Gastrointestinal Tract toxins and by decreasing levels of Polyamines – substances implicated in Psoriasis).
    Evening Primrose and Skin Issues
    Dose-dependent effects of evening primrose oil in children and adolescents with atopic dermatitis.
    Chung BY, Kim JH, Cho SI, Ahn IS, Kim HO, Park CW, Lee CH.
    Previous clinical trials with evening primrose oil in atopic dermatitis (AD) treatment have shown different results. In addition, the optimal dose and duration of treatment with evening primrose oil have not yet been determined.
    The aim of this study is to investigate the dose-response treatment effects of evening primrose oil on clinical symptoms of AD and serum concentrations of polyunsaturated fatty acids.
    Forty AD patients were enrolled for the study and randomly divided into 2 groups: those who received evening primrose oil 160 mg daily for 8 weeks and those who received 320 mg of evening primrose oil twice daily for 8 weeks. We evaluated the Eczema Area Severity Index (EASI) scores of all AD patients at weeks 0, 2, 4 and 8. In addition, we measured the levels of serum fatty acids, including C16 : 0 (palmitic), C18 : 2n (linoleic), C18 : 3n (linolenic) and C20 : 4 (arachidonic acid) using gas chromatography.
    The serum fatty acid levels C18 : 3n and C20 : 4 were higher in the 320 mg group than in the 160 mg group, with statistical significance. After evening primrose oil treatment, EASI scores were reduced in the 2 groups. The improvement in EASI scores was greater in the 320 mg group than in the 160 mg group. There were no side effects seen in either group during the study in the 2 groups.
    The results of this study suggest that the 320 mg and 160 mg groups may be equally effective in treating AD patients and show dose-dependent effects on serum fatty acid levels and EASI scores.
    Environmental transformations of silver nanoparticles- impact on stability and toxicity.
    Levard C, Hotze EM, Lowry GV, Brown GE Jr.
    Author information
    Silver nanoparticles (Ag-NPs) readily transform in the environment, which modifies their properties and alters their transport, fate, and toxicity. It is essential to consider such transformations when assessing the potential environmental impact of Ag-NPs. This review discusses the major transformation processes of Ag-NPs in various aqueous environments, particularly transformations of the metallic Ag cores caused by reactions with (in)organic ligands, and the effects of such transformations on physical and chemical stability and toxicity. Thermodynamic arguments are used to predict what forms of oxidized silver will predominate in various environmental scenarios. Silver binds strongly to sulfur (both organic and inorganic) in natural systems (fresh and sea waters) as well as in wastewater treatment plants, where most Ag-NPs are expected to be concentrated and then released. Sulfidation of Ag-NPs results in a significant decrease in their toxicity due to the lower solubility of silver sulfide, potentially limiting their short-term environmental impact. This review also discusses some of the major unanswered questions about Ag-NPs, which, when answered, will improve predictions about their potential environmental impacts. Research needed to address these questions includes fundamental molecular-level studies of Ag-NPs and their transformation products, particularly Ag(2)S-NPs, in simplified model systems containing common (in)organic ligands, as well as under more realistic environmental conditions using microcosm/mesocosm-type experiments. Toxicology studies of Ag-NP transformation products, including different states of aggregation and sulfidation, are also required. In addition, there is the need to characterize the surface structures, compositions, and morphologies of Ag-NPs and Ag(2)S-NPs to the extent possible because they control properties such as solubility and reactivity.
    TOP B
    TOP C
    Show of the Month February 22 2014
    Chemical constituents, antifungal and antioxidative effects of ajwain
    Biological activity of liposomal vanillin
    It’s All Coming Back to Me Now: Researchers Find Caffeine Enhances Memory
    Dietary levels of pure flavonoids improve spatial memory
    Chemical constituents, antifungal and antioxidative effects of ajwain essential oil and its acetone extract.
    Singh G, Maurya S, Catalan C, De Lampasona MP.
    Author information
    GC and GC-MS analysis of ajwain essential oil showed the presence of 26 identified components which account for 96.3% of the total amount. Thymol (39.1%) was found as a major component along with p-cymene (30.8%), gamma-terpinene (23.2%), beta-pinene (1.7%), terpinene-4-ol (0.8%) whereas acetone extract of ajwain showed the presence of 18 identified components which account for 68.8% of the total amount. The major component was thymol (39.1%) followed by oleic acid (10.4%), linoleic acid (9.6%), gamma-terpinene (2.6%), p-cymene (1.6%), palmitic acid (1.6%), and xylene (0.1%). Moreover, the oil exhibited a broad spectrum of fungitoxic behavior against all tested fungi such as Aspergillus niger, Aspergillus flavus, Aspergillus oryzae, Aspergillus ochraceus, Fusarium monoliforme, Fusarium graminearum, Pencillium citrium, Penicillium viridicatum, Pencillium madriti, and Curvularia lunata as absolute mycelial zone inhibition was obtained at a 6-microL dose of the oil. However, the acetone extract showed better antioxidative activity for linseed oil as compared with synthetic antioxidants such as butylated hydroxyl toluene and butylated hydroxyl anisole.—
    Ajwain -Trachyspermum ammi.
    Bairwa R, Sodha RS, Rajawat BS.
    Author information
    Trachyspermum ammi commonly known as ‘Ajwain’ is distributed throughout India and is mostly cultivated in Gujarat and Rajasthan. The fruit possesses stimulant, antispasmodic and carminative properties and is used traditionally as an important remedial agent for flatulence, atonic dyspepsia, diarrhea, abdominal tumors, abdominal pains, piles, and bronchial problems, lack of appetite, galactogogue, asthma and amenorrhoea. Medicinally, it has been proven to possess various pharmacological activities like antifungal, antioxidant, antimicrobial, antinociceptive, cytotoxic, hypolipidemic, antihypertensive, antispasmodic, broncho-dilating actions, antilithiasis, diuretic, abortifacient, antitussive, nematicidal, anthelmintic and antifilarial. Further, studies reveal the presence of various phytochemical constituents mainly carbohydrates, glycosides, saponins, phenolic compounds, volatile oil (thymol, γ-terpinene, para-cymene, and α- and β-pinene), protein, fat, fiber and mineral matter containing calcium, phosphorous, iron and nicotinic acid. These studies reveal that T. ammi is a source of medicinally active compounds and have various pharmacological effects; hence, it is encouraging to find its new therapeutic uses.
    Ajowan is the small seed-like fruit similar to that of the bishop’s weed (Ammi majus) plant. Because of their seed-like appearance, the fruit pods are
    sometimes called ajwain seeds. Raw ajwain smells like thyme, it also tastes like thyme (or caraway); probably because of its high content of thymol.
    Because a small amount of raw ajwain will completely dominate the flavor of a dish, in Indian cuisine, dry-roasted or fried ajwain is used. [Wikipeida,
    2011] An acetone extract of ajowan contains thymol (39.1%), oleic acid (10.4%), linoleic acid (9.6%), gamma-terpinene (2.6%), p-cymene (1.6%), palmitic acid (1.6%), and xylene (0.1%). [1]–
    Related Names: Ajowan, ajwain, carom seeds, Trachyspermum ammi
    Ajowan Health Benefits
    the chemopreventive effect of different doses (2%, 4%, and 6%) of test diets of Ajowan seeds were examined on DMBA-induced skin and B(a)P-induced forestomach papillomagenesis. Results exhibited a significant reduction in the skin as well as the forestomach tumor multiplicity with respect to all doses of test diet as compared to the control group. Ajowan seed extracts may have benefit on people at risk of certain cancers, but more studies are needed to confirm the
    findings. [A4]
    Dental Caries
    An active compound of Ajowan was found effective against adherent cells of Streptococcus mutans, a major causal organism of dental caries, reduced water-insoluble glucan synthesis and inhibited the reduction in pH. [A2]
    Ajowan oil may benefit people at risk of diarrhea. Interviews with 208 mothers of children aged under 5 years were conducted in 21 villages of Jaipur District in Rajasthan State, India, researchers found that the major herbal medicines used to cure diarrhea were isabgol ke bhusi mixed with curd (31.3%) and extracts of tea leaves, ajwain, sonth, peepla mul, black pepper, and tulsi leaves (14.4%). [2]
    Ajowan oil extracts showed benefits of antifungal activities in an in vitro study. Ajowan oil exhibited a broad spectrum of fungitoxic behavior against all tested fungi such as Aspergillus niger, Aspergillus flavus, Aspergillus oryzae, Aspergillus ochraceus, Fusarium monoliforme, Fusarium graminearum, Pencillium citrium, Penicillium viridicatum, Pencillium madriti, and Curvularia lunata. [3]
    Ajowan showed benefits of liver protection in an animal study. Six groups of rats were maintained for 12 weeks as (1) Control; (2) hexachlorocyclohexane (HCH; 300 mg/kg body weight) injected (3) 1% ajwain extract incorporated diet (4)1% ajwain extract incorporated diet+HCH (5) 2% ajwain extract incorporated diet and (6) 2% ajwain extract incorporated diet+HCH. Results revealed that HCH administration lead to an increase in hepatic lipid peroxidation associated with reduction in, levels of glutathione (GSH), activity of superoxide dismutase (SOD), catalase and glucose-6-phosphate dehydrogenase. Prefeeding of ajwain extract resulted in decreased hepatic levels of lipid peroxides and increased GSH, GSH-peroxidase, G-6-PDH, SOD, catalase and glutathione S-transferase (GST) activities. [4]
    Microbes, Multidrug Resistant
    Ajowan may benefit patients suffered from infections caused by multidrug resistant microbes. A petroleum ether fraction of T. ammi (least MIC- 625 microg/ml) showed efficacy against multidrug resistant microbes. However, more studies are needed to develop it as an anti-microbial agent. [A3]
    Sperm treated with Ajowan essential oil showed a significant decrease in viability. Moreover, the treated sperm also showed a significant loss of functional mitochondria and antioxidant enzyme, catalase, when compared to control. The
    cholesterol:phospholipid ratio was also increased in treated sperm when compared to control, which is an indicator of loss of binding ability of human spermatozoa to the zona pellucida. The scanning electron microscopic studies
    demonstrated the loss of membrane integrity in essential oil-treated human spermatozoa, which showed vacuolation, swelling of acrosomal cap, detachment of head portion and tail coiling. Thus, Ajowan essential oil may be used as male contraceptive, but more studies are needed to determine how to apply it as a contraceptive. [A1]
    Recently, an anticalcifying protein from the seeds of Ajowan Sprague ex Turril (Umbelliferae) deciphered its inhibitory activity against calcium oxalate crystal growth. The antilithiatic activity of the Ajowan anticalcifying protein was also shown in an urolithiatic rat model. A5
    Ajowan Safety Issues and Side Effects
    Though roasted ajowan have been used in Indian cuisine for many year, research studies on ajowan are limited, its side effects and toxicity are unclear.
    Other Potential Uses of Ajowan
    Strong insecticidal activity was observed with the essential oils of Ajowan. A6
    1. Singh G et al J Agric Food Chem. 2004 Jun 2;52(11):3292-6. [2] Indian Pediatr. 1994 Mar;31(3):340-3] [3] J Agric
    Food Chem. 2004 Jun 2;52(11):3292-6.] [4] Anilakumar KR et al, Food Chem Toxicol. 2009 Feb;47(2):279-82] A1 Paul
    S, Kang SC. Studies on the viability and membrane integrity of human spermatozoa treated with essential oil of
    Trachyspermum ammi (L.) Sprague ex Turrill fruit. Andrologia. 2011 Jun 15. A2 Khan R, et al, Novel compound from
    Trachyspermum ammi (Ajowan caraway) seeds with antibiofilm and antiadherence activities against Streptococcus
    mutans: a potential chemotherapeutic agent against dental caries. J Appl Microbiol. 2010 Dec;109(6):2151-9. A3 Khan
    R. et al, Activity of solvent extracts of Prosopis spicigera, Zingiber officinale and Trachyspermum ammi against
    multidrug resistant bacterial and fungal strains. J Infect Dev Ctries. 2010 Jun 3;4(5):292-300. A4 Singh B et al,
    Chemomodulatory effect of Trachyspermum ammi on murine skin and forestomach papillomagenesis. Nutr Cancer.
    2010;62(1):74-84. A5 Kaur T et al, In vivo efficacy of Trachyspermum ammi anticalcifying protein in urolithiatic rat
    model. J Ethnopharmacol. 2009 Dec 10;126(3):459-62..A6 Seo SM et al, Fumigant antitermitic activity of plant essential
    oils and components from Ajowan ( Trachyspermum ammi ), Allspice ( Pimenta dioica ), caraway ( Carum carvi ), dill (
    Anethum graveolens ), Geranium ( Pelargonium graveolens ), and Litsea ( Litsea cubeba ) oils against Japanese
    termite ( Reticulitermes speratus Kolbe). J Agric Food Chem. 2009 Aug 12;57(15):6596-602.
    Arthritis- Do massage with it’s oil on affected joints.
    Flu- 3 gm. ajowan + 3gm cinnamon = boil with water, filter & drink or 12 gm ajowan boil in 2 cup of water ,till remain half, filter & drink.
    cough and cold- 1 tsp ajowan + 4 tsp jaggery boil in 1 glass of water, for 15 mins. filter and drink , sleep with cover.
    Chronic fever- 15 gm ajowan soak in water of mud-pot. Keep insight of home at night and in open at day time.
    Dyspepsia, Rhumetism,Urticaria , Worms= 1tsp ajowan+ salt (according to taste) take with water in the morning empty stomach.
    Digestive powder- Ajowan +Termenalia chebula(Harad,)=equal quantity, asafoetida( heeng)+ saindhav salt(Kind of Salt, which we can use in vrat-upwas) = according to taste, grind to all.take with lukewarm water after meal .
    Stone, calculus- 6 gm ajowan take daily.
    Acne- Grind 30 gm ajowan , mix in 25gm curd & again grind,use it locally at night and wash with lukewarm water to face in the morning.
    Menorrhagia- Soak 25 gm ajowan in mud pot with full of water , whole night.Grind it & drink in the morning.
    Urticaria- Ajowan 1gm+ jaggery 3gm = eat them.
    Biological activity of liposomal vanillin.
    J Med Food. 2013 Jun;16(6):551-7
    Authors: Castan L, Del Toro G, Fernández AA, González M, Ortíz E, Lobo D
    This article presents a study of vanillin encapsulation inside multilamellar liposomes, with emphasis on the evaluation of antioxidant activity, the hemolytic effect, and the antisickling properties of these products. Egg phosphatidylcholine-cholesterol and egg phosphatidylcholine-cholesterol-1-O-decylglycerol liposomes were prepared by mechanical dispersion, all with vanillin included. Vesicles were characterized by determination of encapsulation efficiency and vanillin retention capacity. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The hemolytic effect of liposomes was also evaluated by spectrophotometry, as well as the antisickling activity by the Huck test using optical microscopy. Results showed that the lipid composition of liposomes did not significantly affect the encapsulation efficiency. Stable vesicles were obtained with a high retention percentage of vanillin. Liposomes exhibited a high capture of the DPPH radical compared to free vanillin and 1-O-decylglycerol (C10) in solution. Vesicles caused no significant hemolisys in normal erythrocytes, nor in those coming from patients with sickle cell anemia. Vanillin encapsulated in liposomes retained its antisickling activity, with a greater effect for C10-containing vesicles. Our results show that vanillin encapsulation in liposomes is a way to enhance the pharmacologic properties of this molecule using a suitable vehicle.—PMID: 23767864 [PubMed – indexed for MEDLINE]
    It’s All Coming Back to Me Now: Researchers Find Caffeine Enhances Memory
    New research shows that caffeine enhances certain memories at least up to 24 hours after it is consumed.
    Regardless of the routine, the consumption of caffeine is the energy boost of choice for millions to wake up or stay up. Now, however, researchers at the Johns Hopkins University have found another use for the stimulant: memory enhancer.–Michael Yassa, assistant professor of psychological and brain sciences in the Krieger School of Arts and Sciences at Johns Hopkins, and his team of scientists found that caffeine has a positive effect on long-term memory in humans. Their research, published by the journal Nature Neuroscience, shows that caffeine enhances certain memories at least up to 24 hours after it is consumed.–“We’ve always known that caffeine has cognitive-enhancing effects, but its particular effects on strengthening memories and making them resistant to forgetting has never been examined in detail in humans,” said Yassa, senior author of the paper. “We report for the first time a specific effect of caffeine on reducing forgetting over 24 hours.”–The Johns Hopkins researchers conducted a double-blind trial; which participants who did not regularly eat or drink caffeinated products received either a placebo or a 200-milligram caffeine tablet five minutes after studying a series of images. Salivary samples were taken from the participants before they took the tablets to measure their caffeine levels. Samples were taken again one, three and 24 hours afterwards.–The next day, both groups were tested on their ability to recognize images from the previous day’s study session. On the test, some of the visuals were the same as from the day before, some were new additions and some were similar but not the same as the items previously viewed. More members of the caffeine group were able to correctly identify the new images as “similar” to previously viewed images versus erroneously citing them as the same.–The brain’s ability to recognize the difference between two similar but not identical items, called pattern separation, reflects a deeper level of memory retention, the researchers said.–“If we used a standard recognition memory task without these tricky similar items, we would have found no effect of caffeine,” Yassa said. “However, using these items requires the brain to make a more difficult discrimination — what we call pattern separation, which seems to be the process that is enhanced by caffeine in our case.”–The memory center in the human brain is the hippocampus, a seahorse-shaped area in the medial temporal lobe of the brain. The hippocampus is the switchbox for all short-term and long-term memories. Most research done on memory — the effects of concussions in athletics to war-related head injuries to dementia in the aging population — are focused on this area of the brain.–Until now, caffeine’s effects on long-term memory had not been examined in detail. Of the few studies done, the general consensus was that caffeine has little or no effect on long-term memory retention.-The research is different from prior experiments because the subjects took the caffeine tablets only after they had viewed and attempted to memorize the images.–“Almost all prior studies administered caffeine before the study session, so if there is an enhancement, it’s not clear if it’s due to caffeine’s effects on attention, vigilance, focus or other factors. By administering caffeine after the experiment, we rule out all of these effects and make sure that if there is an enhancement, it’s due to memory and nothing else,” said Yassa.–According to the U.S. Food and Drug Administration, 90 percent of people worldwide consume caffeine in one form or another. In the United States, 80 percent of adults consume caffeine every day. The average adult has an intake of about 200 milligrams — the same amount used in the Yassa study — or roughly one strong cup of coffee or two small cups of coffee per day.–Yassa’s team completed the research at Johns Hopkins before his lab moved to the University of California-Irvine at the start of this year.–“The next step for us is to figure out the brain mechanisms underlying this enhancement,” he said. “We can use brain-imaging techniques to address these questions. We also know that caffeine is associated with healthy longevity and may have some protective effects from cognitive decline like Alzheimer’s disease. These are certainly important questions for the future.”–The lead author of the paper is Daniel Borota, an undergraduate student in Yassa’s lab who received an undergraduate research award from Johns Hopkins to conduct the study. Additional authors, all from Johns Hopkins, are: Elizabeth Murray, a research program coordinator in the Department of Psychological and Brain Sciences; John Toscano, professor in the Department of Chemistry; Gizem Kecili, a graduate student also in the Chemistry Department and Allen Chang, Maria Ly and Joseph Watabe, all undergraduates in the Department of Psychological and Brain Sciences.–This research was supported by grants number P50 AG05146 and R01 AG034613 from the National Institute on Aging as well as CHE-1213438 from the National Science Foundation.— Story Source-The above story is based on materials provided by Johns Hopkins. The original article was written by Latarsha Gatlin. — Journal Reference-Daniel Borota, Elizabeth Murray, Gizem Keceli, Allen Chang, Joseph M Watabe, Maria Ly, John P Toscano, Michael A Yassa. Post-study caffeine administration enhances memory consolidation in humans. Nature Neuroscience, 2014; DOI: 10.1038/nn.3623
    Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor.
    PLoS One. 2013;8(5):e63535
    Authors: Rendeiro C, Vauzour D, Rattray M, Waffo-Téguo P, Mérillon JM, Butler LT, Williams CM, Spencer JP
    Evidence suggests that flavonoid-rich foods are capable of inducing improvements in memory and cognition in animals and humans. However, there is a lack of clarity concerning whether flavonoids are the causal agents in inducing such behavioral responses. Here we show that supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberry (2% w/w), results in an enhancement of spatial memory in 18 month old rats. Pure flavanols and pure anthocyanins were observed to induce significant improvements in spatial working memory (p = 0.002 and p = 0.006 respectively), to a similar extent to that following blueberry supplementation (p = 0.002). These behavioral changes were paralleled by increases in hippocampal brain-derived neurotrophic factor (R = 0.46, p<0.01), suggesting a common mechanism for the enhancement of memory. However, unlike protein levels of BDNF, the regional enhancement of BDNF mRNA expression in the hippocampus appeared to be predominantly enhanced by anthocyanins. Our data support the claim that flavonoids are likely causal agents in mediating the cognitive effects of flavonoid-rich foods.-PMID: 23723987 [PubMed – indexed for MEDLINE]
    Galangin-Bee Propolis
    Horseradish 1.58 Lovage (leaves) 7.0
    Parsley 0.44 Dill 13.33
    Tarragon 11.0 Tea (black) (dry leaf) 126.96
    Tea (green) (dry leaf) 151.9
    Onions (white) 30
    Onions (red) 19.93 Spring Onions 14.24
    Apples 25 Grapes (black) 2.54
    Grapes (red) 3.54 Grapes (green) 0.87
    Grapefruit 0.5 Cranberry 14.02
    Blackcurrants 5.69 Red Currants 4.95
    Elderberry 42.0 Lemon (without peel) 2.29
    Limes 0.4 Lingonberry 12.16
    Pears 0.42 Plums 1.2
    Raspberry 0.83 Strawberry 0.65
    Herbs: Hawthorn Passion Flower
    Dock 86.2 Horseradish 0.28
    Lovage (leaves) 170.0 Parsley 0.33
    Chilli (hot green) 16.8 Perilla Leaves 0.53
    Dill 55.15 Green Tea (dry leaves) 255.55
    Tarragon 10.0 Black Tea (dry leaves) 204.66
    Chickweed Hawthorn
    Peppermint Yerbamate
    Vegetables: Garlic Fennel
    TOP C
    [F1]Up 2 oz in about 50 gallon bath ( give or take )
    [F2]Gamma Radiation Blocker
    [F3]60 grams= 2.1 oz or ½ cup of salt
    [F4]Gentically Determined Skin Disease—this would be connected to Genetically Modifiying the DNA which would have to come from the Food or Vaccines
    [F5]Meaning this is something both genders are exposed to
    [F6]This would require a constant use of either supplements of therapies
    [F7]UV thereapies or sunlight Therapies
    this what is utilized medicinally [F8]—what also can be used as a topical as a mixture of peanut oil or even a olive oil mixed with turpentine —or a simple topical of evening primrose oils that will assist in either regulating skin or hormona balance required for cellular health
    The side efects of cortisteroid usage for this condition just exasberates the condition and is doing nothing but suppressing the symptoms rather then dealing with the actual cause [F9]
    [F10]Best thing to do with this is to dissolve the Vitamin D in a solution of say kerosene or dmso and then mix this with a lanolin til smooth –when applying this as a topical should penetrate and increase uptake of the D vitamin
    Retinoids ==Vitamin A derived materials [F11]